In general, this research is aimed at obtaining information that should make it possible to delineate some of the characteristics of a tumor system in which a low dose of melphalan is curative at an advanced stage of tumor growth. We know already that the curative effectiveness of a low dose of melphalan for mice bearing a large MOPC-315 plasmacytoma depends on the contribution of antitumor immunity in tumor eradication. We will determine whether a low dose of melphalan is curative also for mice bearing a large tumor of selected plasmacytomas that differ in their immunogenicity, thus eliciting varying degrees of antitumor immunity that can contribute to tumor eradication. It is important to further characterize the suppressor cells that operate in the MOPC-315 tumor system, since melphalan leads to selective elimination of their immunosuppressive activity, thereby allowing antitumor immunity to aid effectively in tumor eradication. Particular emphasis will be put on determining: (1)\whether, in addition to macrophage and metastatic tumor cell-mediated immunosuppression, suppressor T cells are also active in the MOPC-315 tumor system; (2)\the dependency of macrophage-mediated suppression of antitumor immune responsiveness on the presence of metastic tumor cells; and (3)\the specificity of the immunosuppression. We will study the mechanism of melphalan-mediated selective elimination of suppressor-cell activity and determine whether the drug acts on the immune system, which in turn eliminates the activity of the suppressor cells. Subsequently, we will determine whether melphalan-mediated selective elimination of suppressor-cell activity is peculiar to the MOPC-315 tumor system or also occurs in other tumor systems in which the reduced antitumor-immune responsiveness is due to: (1)\macrophage-mediated suppression; (2)\macrophage-mediated suppression in the presence of metastatic tumor cells that are or are not highly sensitive to the tumoricidal activity of melphalan; and (3)\suppressor T cells. The results obtained should shed light on the characteristics of suppressor cells whose activity can be selectively eliminated by melphalan and the nature of help provided by the immune system for the eradication of a large tumor by a low dose of drug. Such information should make it possible to identify tumor systems in which low-dose chemotherapy can be effective at a late stage of tumor growth. (HF)